Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile

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Abstract
Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality. To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures. The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset cultures proven sepsis from 1991-1998. The second phase (S2) was a prospective study that enrolled infants > or = 72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis. S1: Of the 48 episodes of culture proven, late-onset sepsis, 54% of the blood cultures were positive by 24 hours and 90% by 48 hours. The most common presenting signs were desaturations (50%) and increased gastric residuals (33%); I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile, as compared to those with no sepsis. Seven (88%) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs. 13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different. In both S1 and S2, a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.